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Breaking cardiovascular risk with ACE inhibitors
- 1. Breaking the cardiovascular risk continuum: New evidence with ACE inhibitors Presentation by : Sri.K.Narsing.Rao
- 2. …At an average age of 42 years…the prevalence of common risk factors other than hypertension in India… 17 64 38 33 Diabetes >Lipids Smoking LVH Populationfrequency% …with 47% having at least 2 risk factors… Nat Med J India, 2005; 18: 59-65.
- 3. Each Additional Risk Factor Substantially Increases Risk of a Cardiovascular Event … 6 7.1 12 18.8 24.7 44.8 10yearCVDeventrisk% … In a 42 year old Indian male… No risk factor + > BP +Smoking + Lipids + Diabetes + LVH Nat Med J India, 2005; 18: 59-65.
- 4. Significant reduction in CV mortality 0.0 1.0 2.0 3.0 4.0 5.0 Years 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 Amlodipine/Perindopril Atenolol ± thiazide P= 0.001 24%24% Lancet 2005; 366: 895–906.
- 5. Amlodipine ± perindopril better Atenolol ± thiazide better 0.50 0.70 1.00 1.45 Secondary Total coronary end point Total CV event and procedures All-cause mortality Cardiovascular mortality Fatal and non-fatal stroke Tertiary Unstable angina New-onset diabetes mellitus New-onset renal impairment 2.00 All secondary & tertiary end-points in favor of amlodipine + perindopril Relative risk reduction 13% 16% 11% 24% 23% 30% 15% Lancet 2005; 366: 895–906.
- 6. ACE inhibitors prevent CV events in CAD patients with heart failure AIRE Study Investigators. Lancet. 1993;342:821-8. Køber L et al. N Engl J Med. 1995;333:1670-6. SOLVD Investigators. N Engl J Med. 1991;325:293-302. SOLVD Investigators. N Engl J Med. 1992;327:685-91. Pfeffer MA et al. N Engl J Med. 1992;327:669-77. AIRE TRACE SOLVD (Treatment) SAVE 0.002 0.001 0.0036 0.019 0 5 10 15 20 25 Risk reduction in total mortality (%) 30 SOLVD (Prevention) 0.30 27% 22% 8% 16% 19% P
- 7. Studies confirm the benefits in patients in all types of CAD patients Yusuf S et al. N Engl J Med. 2000;342:154-160. HOPEHOPE Placebo Ramipril P<0.0003 2000150010005000 0.0 0.05 0.1 0.15 Days of follow-up % 22%22% All high risk patients with CADAll high risk patients with CAD
- 8. EUROPA study confirmed the benefits of all types of CAD patients PerindoprilPerindopril PlaceboPlacebo Risk reductionRisk reduction YearsYears 00 22 44 66 88 1010 1212 1414 00 11 22 33 44 P<0.0003P<0.0003 EUROPA study, Lancet, 2003;362:782-788. (%)(%) 20%20% ACE inhibitor perindoprilACE inhibitor perindopril Prevents MI, CV death & cardiac arrestPrevents MI, CV death & cardiac arrest
- 9. Guidelines recommend ACE inhibitors in Stable angina
- 10. Short-term trials confirm the benefits of ACE inhibitors Odds ratio (95% CI) 220/3044 (7.23%) 570/9682 (5.89%) 2035/29,028 (7.01%) 676/7460 (9.06%) CONSENSUS-II* Test for Heterogeneity: χ2 5.8 (2p = 0.1) df = 3 Deaths (n) GISSI-3 ISIS-4 CCS-1 Total ControlControl 1.0 1.25 1.50.750.5 727/7489 (9.71%) 650/9712 (6.69%) 192/3046 (6.30%) 2171/29,022 (7.48%) 3501/49,214(7.11%) 3740/49,269 (7.59%) ACEIACEI ACEI better Control better Treat Eff: χ2 (2p = 0.004) ACE Inhibitor MI Collaborative Group. Circulation. 1998;97:2202-12. * IV infusion followed by oral therapy Randomized (n)
- 11. Same confirmed in long-term trials with ACE inhibitors Flather M Lancet 2000;355:1575-81Flather M Lancet 2000;355:1575-81 0.5 1 1.5 2 Mortality Death + re-infarction Re-infarction Death + MI+ Re-admission HF P <0.0001 P=0.0057 P<0.0001 P<0.0001 ACEI better Placebo better 0.740.74 0.800.80 0.750.75 0.750.75 SAVE – AIRE – TRACE 5966 patientsSAVE – AIRE – TRACE 5966 patients
- 12. Class I 1. An ACE inhibitor should be administered orally within the first 24 hours of STEMI to patients with anterior infarction, pulmonary congestion, or LVEF less than 0.40, in the absence of hypotension (Level of Evidence: A) ACC/AHA Guidelines for the Management of Patients With ST- Elevation Myocardial Infarction
- 13. An ACE inhibitor administered orally within the first 24 hours of STEMI can be useful in patients without anterior infarction, pulmonary congestion, or LVEF less than 0.40 in the absence of hypotension. (Level of Evidence: B) ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction
- 14. PROGRESS collaborative group, Lancet 2001;358:1033-41. -28 -24 -50 -60 -45 -30 -15 0 Total stroke Ischaemic stroke Haemorrohagic stroke %riskreduction ……Perindopril prevents cerebrovascular eventsPerindopril prevents cerebrovascular events ACE inhibitors prevent recurrent stroke
- 15. Guidelines recommend ACE inhibitors in Recurrent stroke prevention JNC 7 refers to PROGRESS study Latest ASA / ASH refers to PROGRESS study
- 16. Overview of ACE inhibitors in heart failure 5 Cumulative mortality (%) 40 30 20 10 0 0 1 2 3 4 Time since randomisation (years) All trials ACE-I Placeb0 6391 6372 5378 5279 4204 4025 2457 2364 892 742 Flather et al. Lancet 2000; 355: 1575-81
- 17. ESC guidelines on CHF “ACE inhibitors are recommended as first line therapy in all patients, with or without symptoms, who have a reduced LVEF (< 40 or 45%)…to improve survival, symptoms, functional capacity, and reduce hospitalization.” Level of evidence A, Class of recommendation 1 Swedberg K et al. Eur Heart J 2005; 26: 115-1140.
- 18. ACE inhibitors have different… Ferrari ExpRCT. 2205; 3; 15-29 … pharmacological and clinical properties Captopril Fosinopril Enalapril Lisinopril Ramipril Trandolapril Perindopril
Editor's Notes
- This is because recent data confirms our clinical experience, that our hypertensives are younger and we are at increased risk of developing of cardiovascular disease. In a country like ours the role of prescribed therapy is all the more important as it should be able to slow down or prevent the progression of cardiovascular disease.
- We all know that the presence of risk factors significantly increases the overall risk for cardiovascular events. In this scenario the drugs we use should be effective across the spectrum of cardiovascular disease. The two most widely studied drug classes in the recent years to have a significant impact on the cardiovascular continuum are ACE inhibitors and Statins.
- Despite similar blood pressure reduction amlodipine+perindopril group produced a significant and superior 24% reduction in CV mortality as compared to betablocker+diuretic arm.
- What ever the end point we take this was in favor of Amlodipine + perindopril group.
- Based on these trials ACE inhibtors in general are recommended in all CAD patients with LV dysfunction What about CAD patients without LV dysfunction. Two land mark trials HOPE and EUROPA have demonstrated the benefits of ACE inhibitors in CAD patients even without LV dysfunction.
- The HOPE trial confirmed the benefits of ramipril in CAD patients without LV dysfunction. However, the evidence was in CAD patients at high levels of risk.
- The subsequent EUROPA trial with perindopril has bridged the gap by involving patients at all levels of risk. Treatment with perindopril reduced the relative risk of cardiovascular death, non-fatal MI or cardiac arrest by 20%. This reduction was seen on top of optimal therapy like aspirin, statin and all other seconadry preventive therapies.
- Based on the evidence from these two land mark trials the latest ESC guidelines on stable angina recommend ACE inhibitors in all CAD patients
- Short term trials with ACE inhibitors have confirmed the benefits of ACE inhibitors in patients of Acute myocardial infarction.
- The chronic usage of ACE inhibitors also results in significant reduction in myocardial infarction and death. However majority of these studies are performed in patients with low ejection fraction. What about AMI patients with preserved ejection fraction.
- Please read the slide
- Please read the slide
- In prevention of secondary stroke, perindopril has the distinction of being the only ACE inhibitor having the evidence in a large clinical specially done in patients with recurrent stroke. Treatment with perindopril on top of optimal therapies led to a significant reduction in all types of stroke including the risk of hemorrhagic stroke.
- Based on the evidence from the PROGRESS study ACE inhibitors are recommended in the management of stroke.
- All patients with heart failure due to left ventricular systolic dysfunction should be considered for treatment with an ACE inhibitor.Treatment should be instituted before beta-blockade is introduced. A prospective systematic overview, based on data from individual patients from five long-term randomised trials that assessed ACE inhibitors in 12,763 patients with left-ventricular dysfunction or heart failure, has demonstrated that the ACE inhibitor group had: Reduced the rates of death, reinfarction and readmission. These benefits were observed early after the start of therapy and persisted long term.The benefits of treatment on all outcomes were independent of age, sex, and baseline use of diuretics, aspirin, and beta-blockers.
- Please read the slide
- Please read the slide
- They have different acceptability profile, so they differ on there effects on clinical outcomes. We need to use only evidence based ACE inhibitors in clinical practice.